Molecular characterization of the new clinical entity associated with congenital adrenal hyperplasia: the CAH-X syndrome in the Spanish population

Abstract

Abstract Objectives The chimeras causing the CAH-X syndrome (SCAH-X) result from recombination between CYP21A2-TNXB and their respective pseudogenes (CYP21A1P-TNXA). The clinical manifestations of this syndrome include congenital adrenal hyperplasia (CAH) and Ehlers–Danlos syndrome (EDS). Since SCAH-X has been recently described, the number of publications available is limited. The objective of this study was to set up a molecular approach and a screening algorithm for detecting CAH-X chimeras, determine their frequency and distribution in the Spanish population, and assess their clinical pattern of occurrence in a group of patients. Methods A total of 186 patients were eligible for CAH-X molecular genetic testing. Testing included MLPA, heterodimer detection by capillary gel electrophoresis, and sequencing of exons 40, 41, and 43 of TNXB. A review was performed of the medical history of 20 patients from three hospitals of reference and the signs and symptoms of EDS they exhibited. Results In total, 78 CAH patients were carriers of CAH-X chimeras (41.9 %). Forty-six patients were carriers of CH1 (24.7 %), 24 of CH2 (12.9 %), and 8 of CH3 (4.3 %), with a heterogeneous geographical distribution. Seven (35 %) of the 20 carriers of a CAH-X chimera who underwent clinical examination experienced clinical manifestations of EDS. Conclusions The impact of SCAH-X in the Spanish population was assessed by genetic testing. In the light of the clinical pattern of occurrence and significant prevalence of SCAH-X in the Spanish population, early diagnosis of this entity is essential for an appropriate follow-up of clinical manifestations.